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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 33  |  Issue : 3  |  Page : 302-306

Prevalence of preeclampsia among human immunodeficiency virus-positive pregnant women as compared to human immunodeficiency virus-negative women in Ibadan


1 Department of Obstetrics and Gynaecology, University College Hospital, Ibadan, Nigeria
2 Department of Obstetrics and Gynaecology, University College Hospital; Department of Obstetrics and Gynaecology, College of Medicine, University of Ibadan, Ibadan, Nigeria

Date of Web Publication8-Feb-2017

Correspondence Address:
R O Olayide
Department of Obstetrics and Gynaecology, University College Hospital, Ibadan
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0189-5117.199809

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  Abstract 

Introduction: Preeclampsia is a common complication of pregnancy and a major cause of maternal morbidity. Pathogenetic explanations for preeclampsia include: Maladaptation of the immune system to paternal antigens and exaggerated maternal inflammatory response to trophoblastic tissue. Immune deficiency, induced by human immunodeficiency virus (HIV) or any other cause, could, therefore, inhibit a tendency to immune hyper-reactivity and thus theoretically prevent the development of preeclampsia. The study aims to explore the role of the immune theory of preeclampsia by comparing the prevalence of preeclampsia among HIV-positive and HIV-negative pregnant women.
Materials and Methods: The study was a cross-sectional survey of pregnant women, beyond 28 weeks gestation, who delivered at the University College Hospital, Ibadan between 1st October 2011 and 31st December 2011. Data was collected using a prespecified proforma. The analysis was performed using SPSS version 17.0 and P value was set at <0.05.
Results: A total of 766 women who gave birth during the study met the inclusion criteria. Among the cohort, HIV prevalence rate was 7.2% whereas preeclampsia was 10.7%. None of the HIV-positive women had preeclampsia.
Conclusion: This study suggested that the prevalence and perhaps, risk of developing preeclampsia is reduced among HIV positive women. This is similar to other studies done in various countries in the world. There is a need for further study as it may prove valuable in the management and prevention of preeclampsia.

Keywords: Human immunodeficiency virus; immune deficiency; preeclampsia; pregnant women.


How to cite this article:
Olayide R O, Oluwasola T, Adesina O A. Prevalence of preeclampsia among human immunodeficiency virus-positive pregnant women as compared to human immunodeficiency virus-negative women in Ibadan. Trop J Obstet Gynaecol 2016;33:302-6

How to cite this URL:
Olayide R O, Oluwasola T, Adesina O A. Prevalence of preeclampsia among human immunodeficiency virus-positive pregnant women as compared to human immunodeficiency virus-negative women in Ibadan. Trop J Obstet Gynaecol [serial online] 2016 [cited 2020 Oct 23];33:302-6. Available from: https://www.tjogonline.com/text.asp?2016/33/3/302/199809


  Introduction Top


Preeclampsia is a common complication of pregnancy and a major cause of maternal morbidity. Although called “disease of theories” because its etiology has remained unclear, preeclampsia is said to be associated with placental disorder, endothelial cell dysfunction, and systemic vasospasm.[1] One famous theory holds maladaptation of the immune system to paternal antigens responsible for the development of preeclampsia.[2] Another theory maintains that preeclampsia results from an exaggerated maternal inflammatory response to trophoblastic tissue.[2] The events leading to these alterations remains unclear, but it seems that abnormal activation of the immune system plays a relevant role in the etiology of preeclampsia.[1]

It has been suggested that infection with human immunodeficiency virus (HIV) may reduce the risk of developing preeclampsia even though only few studies have tried to study the relationship between preeclampsia and HIV infection in pregnancy.[3],[4],[5] Before the advent of highly active antiretroviral therapy (HAART), preeclampsia was uncommon in HIV-positive pregnant women. The incidence of preeclampsia in these women was reported to be lower than in the general population.[5],[6] It has been hypothesized that HAART will theoretically increase the risk of preeclampsia by causing a direct toxic effect on the liver thereby affecting retinoid-related processes which are thought to underlie the development of preeclampsia in HIV-negative pregnancies. However, some recent studies examining the risk of preeclampsia in pregnant women receiving HAART have yielded conflicting results.[7]

It is clear that the current understanding of the relationship between HIV and preeclampsia is based on patchy scientific evidence and is at best speculative. Some evidence suggests that the use of HAART in pregnancy may also increase the risk of adverse fetal outcomes, including preterm birth, low birth weight, and small for gestational age.[8],[9],[10],[11] While some other studies reported no adverse neonatal outcomes with the use of HAART.[12],[13],[14] The main objective of this study was to explore the prevalence of preeclampsia among HIV-positive pregnant women as compared to HIV-negative women in the University College Hospital (UCH), Ibadan and to compare the feto-maternal outcomes in this two groups of patients.


  Materials and Methods Top


Setting

The study was set in Ibadan, the capital of Oyo state, a large urban settlement in South Western Nigeria. UCH is an 880-bed tertiary health institution which also functions as a referral center for hospitals in neighboring regions.

Study population and sampling

This was a cross-sectional survey conducted at the labor ward of the UCH from October 1 to December 31, 2011. The study population included pregnant women who delivered at a gestational age of at least 28 weeks irrespective of the outcome. Booked pregnant women are routinely screened for HIV after due counseling and if confirmed positive are commenced on HAART as part of prevention of mother-to-child transmission strategy. For the unbooked pregnant woman presenting in labor, a rapid screening is usually done, and if reactive the babies are placed on antiretroviral prophylaxis pending confirmatory tests.

A pro forma was used to obtain information on date of delivery, maternal age, gravidity, parity, gestational age at delivery, number of babies, and maternal HIV status for all deliveries at the hospital. Other information included the use of HAART, preexisting co-morbidities, and pregnancy outcomes were ascertained through patient records.

The primary outcome of interest was the development of preeclampsia in HIV positive women. Secondary outcomes were other pregnancy outcomes (such as; preterm births and neonatal outcomes such as neonatal mortality and neonatal morbidity, measured by neonatal intensive care admission). For multi-fetal pregnancies, the birth weight and age of the first-born twin/triplet were used to represent the outcome of the pregnancy in the analysis.

All aspects of this study complied with the Helsinki declaration of the 52nd World Medical Association General Assembly of October 2000.

Statistical analysis

Data were entered, collated, and analyzed using SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc.

Means and standard deviations were computed for continuous variables. Chi-squared test and Fisher's exact test were used for comparison of proportions. A P < 0.05 was considered statistically significant.


  Results Top


A total of 766 deliveries during the study met the inclusion criteria, of which 55 were by HIV-positive women giving a prevalence rate of 7.2%, whereas 76 (10.7%) had preeclampsia.

Baseline obstetric information in the 2 groups of patients is shown in [Table 1]. The age groups and parity are similar in the 2 groups. The majority of HIV-positive patients booked for antenatal care and had at least one dose of intermittent preventive therapy for malaria.
Table 1: Baseline Obstetrics Characteristics

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For the HIV-positive group, CD4 counts were available for 54 (98.1%) of the women, whereas viral load was available for 51 (92.8%). Nine women had acquired immunodeficiency syndrome, on the basis of a CD4 count of <200/mm 3. This is presented as histogram in [Figure 1]. Thirty-eight (69.1%) had an undetectable viral load indicating that they were stable on their medication and effectively suppressing the HIV virus [Figure 2].
Figure 1: Histogram showing the latest CD4 count values among the HIV-Positive women

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Figure 2: Histogram showing the latest viral load values for the HIV-positive women

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Seventy-six (10.7%) women were found to have proteinuric hypertension, and they were all in the HIV negative group, [Table 2]. The corresponding proportions for preeclampsia-eclampsia was 76 (10.7%) in the HIV-negative group compared with none (0%) in the HIV-positive group (Fisher's exact test P = 0.004).
Table 2: Frequency of Preeclampsia-Eclampsia in HIV negative and HIV positive women

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Analysis of the delivery outcomes across the groups [Table 3], revealed a better APGAR scores at 5 min in the HIV positive women (100% vs. 87.8%; P < 0.05). Gestational age at delivery, number of preterm deliveries, birth weights of babies, and neonatal outcomes were similar in the 2 groups. The majority of the HIV Positive women, however, had Cesarean delivery (70.9% vs. 29.1%; P < 0.05).
Table 3: Pregnancy outcomes between HIV positive and HIV negative women

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  Discussion Top


This study explored the prevalence of preeclampsia among the HIV-seropositive women and found none despite an overall 10.7% rate in the study population. It can also be inferred that the use of HAART in HIV-positive pregnant women did not increase the risk of adverse outcomes among the babies.

Prevalence of preeclampsia was significantly low in HIV-seropositive women as found in this study which is similar to the findings of Wimalasundera et al.[5] However, unlike Wimalasundera's study, we included all women delivering in the facility regardless of mode of delivery. Our study strengthens the findings of Matar et al., who conducted a retrospective study and obtained similar results. Our findings are also similar to that of Boyajian et al.[15] who conducted a matched case-control study to minimize the effect of confounders. The prevalence of preeclampsia in the study group was similar to that quoted for developing countries (1.8–16.7%),[16] suggesting a good representative sample.

The immunologic theory of preeclampsia proposes that preeclampsia is triggered when immune tolerance to foreign fetal antigens is not properly established in a pregnant woman, causing poor placentation and a cascade of inflammatory events.[17],[18] According to this theory, a weak immune system could be protective against preeclampsia, as HIV-positive women may be less likely to mount the exaggerated immune response seen in preeclampsia,[5] as is the case in this survey. Another possibility is that HIV infection may inhibit other factors that play a relevant role in preeclampsia development.

The results from this study revealed a slightly lower incidence of preterm births in HIV-positive pregnant women on HAART and in HIV-negative women though this was similar to the matched cohort study by Boyajian et al.[15] It is possible that the sample size in this study was not large enough to clearly identify differences between these two groups and a matched study would have probably clearly evaluated the relationship.

There was also a slightly lower incidence of low birth weight infants in the HIV-positive pregnant women, although this did not reach statistical significance and is unlike the findings of Boyajian et al.,[15] that reported a higher risk of LBW infants for HIV-positive women on HAART. The risk of LBW infants for HIV-positive mothers could be due to HIV infection or to adverse effects of HAARTS. However, this study revealed a higher antenatal care registration and attendance in the HIV positive women. This could be because HIV-positive women receive free health care and are, therefore, more likely to attend antenatal clinic.

This study also revealed better APGAR scores and perinatal outcomes in HIV-exposed infants which could be because majority of the HIV positive women booked for antenatal care early in pregnancy, and had early operative intervention during labor (as there was a higher incidence of caesarean delivery in this group). There was an increased number of neonatal admission among the HIV-exposed babies (7.3 vs. 5.6%;p 0.201), but this could be due to the small sample size of the HIV-positive group. Furthermore, the indication for neonatal admission was more for “presumed” sepsis in the HIV positive group as there was no case of birth asphyxia.

Limitations

This study has some limitations, first of which, is the relatively smaller proportion of the HIV-positive women and the fact that the comparison group consisted of HIV-negative women rather than untreated HIV-positive women. However, this comparison would be unethical.

The study design being a cross-sectional one measures exposure (presence of HIV infection/immune deficiency) and outcome (development of preeclampsia) at the same time. It is the most appropriate design for prevalence studies and every patient presenting at the labor ward for delivery were included in the study eliminating attrition and also recall bias.

The study design does not, however, eliminate systemic differences/confounders in the classification of subjects in each of the exposure groups (the presence or absence of immune deficiency from HIV infection), as would a randomized control trial.


  Conclusion Top


It can be concluded that there is a lower prevalence of preeclampsia in women with HIV infection which may theoretically be due to the suppressed immune response in these group.

HIV-positive women on HAART do not appear to have an increased risk of preeclampsia nor do they have an increased incidence of adverse neonatal outcomes. This emphasizes the overwhelming benefits of HAART for the prevention of perinatal transmission of HIV and improving maternal health outweigh the potential risks.

Further studies should utilize an analytical multi-center approach and investigate the role of immune deficiency using the indices of immunity, such as CD4 counts (as a marker of immune competence or suppression), even in HIV-negative women.

More research would also be beneficial to explore the association between HIV infection, use of antiretroviral drugs and development of preeclampsia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Redman CW, Sacks GP, Sargent IL. Preeclampsia: An excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999;180 (2 Pt 1):499-506.  Back to cited text no. 1
    
2.
Pridjian G, Puschett JB. Preeclampsia. Part 2: Experimental and genetic considerations. Obstet Gynecol Surv 2002;57:619-40.  Back to cited text no. 2
    
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Ellis J, Williams H, Graves W, Lindsay MK. Human immunodeficiency virus infection is a risk factor for adverse perinatal outcome. Am J Obstet Gynecol 2002;186:903-6.  Back to cited text no. 3
    
4.
Mattar R, Amed AM, Lindsey PC, Sass N, Daher S. Preeclampsia and HIV infection. Eur J Obstet Gynecol Reprod Biol 2004;117:240-1.  Back to cited text no. 4
    
5.
Wimalasundera RC, Larbalestier N, Smith JH, de Ruiter A, McG Thom SA, Hughes AD, et al. Pre-eclampsia, antiretroviral therapy, and immune reconstitution. Lancet 2002;360:1152-4.  Back to cited text no. 5
    
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Stratton P, Tuomala RE, Abboud R, Rodriguez E, Rich K, Pitt J, et al. Obstetric and newborn outcomes in a cohort of HIV-infected pregnant women: A report of the women and infants transmission study. J Acquir Immune Defic Syndr Hum Retrovirol 1999;20:179-86.  Back to cited text no. 6
    
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Mawson AR. Effects of antiretroviral therapy on occurrence of pre-eclampsia. Lancet 2003;361:347-8.  Back to cited text no. 7
    
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European Collaborative Study; Swiss Mother and Child HIV Cohort Study. Combination antiretroviral therapy and duration of pregnancy. AIDS 2000;14:2913-20.  Back to cited text no. 8
    
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Thorne C, Patel D, Newell ML. Increased risk of adverse pregnancy outcomes in HIV-infected women treated with highly active antiretroviral therapy in Europe. AIDS 2004;18:2337-9.  Back to cited text no. 9
    
10.
Townsend CL, Cortina-Borja M, Peckham CS, Tookey PA. Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland. AIDS 2007;21:1019-26.  Back to cited text no. 10
    
11.
Grosch-Woerner I, Puch K, Maier RF, Niehues T, Notheis G, Patel D, et al. Increased rate of prematurity associated with antenatal antiretroviral therapy in a German/Austrian cohort of HIV-1-infected women. HIV Med 2008;9:6-13.  Back to cited text no. 11
    
12.
Tuomala RE, Watts DH, Li D, Vajaranant M, Pitt J, Hammill H, et al. Improved obstetric outcomes and few maternal toxicities are associated with antiretroviral therapy, including highly active antiretroviral therapy during pregnancy. J Acquir Immune Defic Syndr 2005;38:449-73.  Back to cited text no. 12
    
13.
Patel K, Shapiro DE, Brogly SB, Livingston EG, Stek AM, Bardeguez AD, et al. Prenatal protease inhibitor use and risk of preterm birth among HIV-infected women initiating antiretroviral drugs during pregnancy. J Infect Dis 2010;201:1035-44.  Back to cited text no. 13
    
14.
Schulte J, Dominguez K, Sukalac T, Bohannon B, Fowler MG; Pediatric Spectrum of HIV Disease Consortium. Declines in low birth weight and preterm birth among infants who were born to HIV-infected women during an era of increased use of maternal antiretroviral drugs: Pediatric spectrum of HIV disease, 1989-2004. Pediatrics 2007;119:e900-6.  Back to cited text no. 14
    
15.
Boyajian T, Shah PS, Murphy KE. Risk of preeclampsia in HIV-positive pregnant women receiving HAART: A matched cohort study. J Obstet Gynaecol Can 2012;34:136-41.  Back to cited text no. 15
    
16.
Osungbade KO, Ige OK. Public health perspectives of preeclampsia in developing countries: Implication for health system strengthening. J Pregnancy 2011;2011:481095.  Back to cited text no. 16
    
17.
Dekker G, Robillard PY. Pre-eclampsia: Is the immune maladaptation hypothesis still standing? An epidemiological update. J Reprod Immunol 2007;76:8-16.  Back to cited text no. 17
    
18.
Luo ZC, An N, Xu HR, Larante A, Audibert F, Fraser WD. The effects and mechanisms of primiparity on the risk of pre-eclampsia: A systematic review. Paediatr Perinat Epidemiol 2007;21 Suppl 1:36-45.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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